Toronto (February 21, 2019) – The Ontario Institute for Cancer Research (OICR) today announced that four Early Accelerator projects from across Ontario will each receive $100,000 for one year as part of OICR’s Cancer Therapeutics Innovation Pipeline (CTIP) initiative. The funding will be used to validate cancer targets and support experiments to screen molecules against these targets, finding those that can bind to them successfully and have potential to be developed into medicines.

The importance of understanding
biological pathways – or how our genes work together – is becoming increasingly
evident, but pathway analysis remains a major challenge for many basic and
biomedical researchers. Current computational tools can help simplify this
analysis, but there is no established guide or standard for using these tools in
practice.

To fill this gap, a
team of experts from OICR and the Bader Lab
at the University of Toronto recently published a comprehensive, step-by-step
guide to pathway enrichment analysis that brings together their highly-recommended
tools into one protocol. The complete protocol, which is now published in Nature Protocols,
can be performed in less than five hours and can be used by researchers with no
prior training in bioinformatics or computational biology.

“These days, almost
every omics study needs to include
pathway enrichment analysis, but it has been over a decade since a
comprehensive protocol for these analyses has been published,” says Dr. Jüri
Reimand, Principal Investigator at OICR and co-lead author of the protocol. “Our
new methods are designed to guide researchers through their analyses and serve
as a practical resource for their studies.”

Each step of the
protocol is supported with detailed instructions and valuable troubleshooting
information, which were designed in large part by Ruth Isserlin, co-lead author
and Senior Bioinformatics Analyst in the Bader Lab.

Recently, the methods
were used to identify a therapeutic
target for ependymoma, a prevalent type of childhood brain
cancer that is notoriously difficult to treat. The pathway analysis, as
described in Nature,
led to a better understanding of why most ependymoma treatments are not
effective and revealed a new treatment option that could stop the progression
of the disease.

“Future cancer
research discoveries rely on our understanding of biological pathways,” says
Reimand. “This protocol provides a resource from which we can build our understanding
and explore previously uncharted relationships between our genes.”

Research has shown that some types of bladder cancer respond well to treatment and other types are resistant, yet molecular subtyping, which can help better define a patient’s cancer and direct them to a more targeted treatment, is not performed in the clinic. This means that patients are often treated with a one-size-fits-all approach. Despite recent research progress, the movement of MIBC subtyping to the clinic has stagnated.

When the first volunteer signed up for the Ontario Health Study (OHS), carefully filling out a detailed online health questionnaire, they no doubt hoped their efforts would do some good. They could never have predicted that, 10 years on, their de-identified health data is now pooled with those of nine million other altruists, from across four continents, in addition to being part of a Canadian national database.

In a contribution to The Globe and Mail titled “For Innovation, open science means business”, E. Richard Gold and Max Morgan point to the recent investment by U.S. pharmaceutical giant Celgene into a potential treatment for leukemia developed by OICR researchers, as an example of how Canada can successfully commercialize its scientific discoveries. The authors note that the uniquely Canadian approach employed by FACIT and OICR working together will, unlike other strategies, keep the intellectual property (IP) in Canada longer and see research and development, clinical trials and other outcomes, benefit Canada and Ontario.

Gold
and Morgan point out that it was an open science collaboration between OICR and
the University of Toronto’s Structural Genomics Consortium (SGC) that allowed
for the initial scientific discovery behind the new potential drug to take
place rapidly, since traditional concerns around IP weren’t a factor. This
approach allowed FACIT and OICR to move towards targeted drug development much
earlier than possible under other models, enabling them to create a patented
drug candidate. Gold and Morgan call on Canadian governments to replicate the
open science to IP model, which Celgene’s investment shows is a viable path to
commercialization in Canada.

OICR’s Adaptive Oncology team has been granted $875,000 from Genome Canada to expand Dockstore – a framework for generating and sharing portable computational biology workflows.

Cancer genomics research depends on the ability to analyze massive datasets in a standardized and coordinated manner. This involves creating and managing workflows – a series of processes and computational tools – that are often long, complex and difficult to share between research groups.

Largest transaction to date for Canadian-discovered preclinical asset arises from Ontario collaborators

TORONTO, ON (January 29, 2019) – Triphase Accelerator, together with its majority shareholder FACIT, today announced a new strategic collaboration with Celgene for a first-in-class preclinical therapeutic targeting the WDR5 protein for the treatment of blood cancers including leukemia. Triphase is a drug development company advancing novel compounds through Phase 2 proof-of-concept, including the WDR5 program.

Years of hard work by OICR’s Drug Discovery group and Ontario partners
moves potential new treatment for leukemia towards clinical trials

On January 29, 2019, Celgene Corporation made an
investment of up to US$1 billion that will facilitate further research and
development of the potential drug and support clinical trials in Ontario. The
potential drug was designed to exploit a weakness in leukemia centred on the
protein WDR5 that was discovered by Ontario researchers. If all options under the investment are
exercised, the deal will be the largest transaction to date for a preclinical
asset discovered in Canada.

“The progress of
this pre-clinical drug towards the clinic is an example of how OICR, working
with its partners, is accelerating cancer research in Ontario and increasing
investment so that new innovations can help patients as soon as possible,” says
Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “This
announcement shows how OICR and FACIT’s unique model for research and
commercialization can generate long-term impact for the province of Ontario.” FACIT
is OICR’s strategic commercialization partner.

The WDR5 project’s development demonstrates the
unique expertise of OICR DD, the advantages to the OICR-FACIT model, and how
OICR effectively harnesses the strengths of Ontario’s diverse cancer research
ecosystem by collaborating with groups such as the Structural Genomics
Consortium (SGC), the group that initially identified the potential of
targeting WDR5 as a treatment for cancer.

TORONTO (January 29, 2019) – A first-of-its-kind therapy for leukemia discovered by researchers in the Ontario Institute for Cancer Research’s (OICR) Drug Discovery Program, and under preclinical development, has attracted investment from Celgene Corporation that could exceed US$1 billion – which would make it the largest transaction to date for a preclinical asset discovered in Canada.

This investment will
allow for clinical trials based in Ontario, and will further research and
development of the drug and other cancer research innovations developed in the
province. The commercialization of this technology was conducted by OICR’s
strategic partner FACIT and demonstrates the realization of the two partners’
long-term vision of creating a sustainable pathway for therapeutic innovation
in Ontario.

“The progress of
this pre-clinical drug towards the clinic is an example of how OICR, working
with its partners, is accelerating cancer research in Ontario and increasing
investment so that new innovations can help patients as soon as possible,” says
Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “Today’s
announcement shows how OICR and FACIT’s unique model for research and commercialization
can generate long-term impact for the province of Ontario.”

The project is
built on the observation that a protein known as MLL-1 plays an important role
in promoting the development of leukemia. It does this through binding with a
partner protein called WDR5. This new therapy works by disrupting the
MLL-1/WDR5 protein-protein interaction, therefore inhibiting the
cancer-promoting activity of the MLL-1 protein.

The possibility of targeting
WDR5 to disrupt the cancer-driving activity of MLL-1 was first suggested by one
of OICR’s partners, the Structural Genomics Consortium (SGC) at the University of Toronto, where
researchers saw its potential and proposed a collaboration with OICR’s Drug
Discovery (DD) program. OICR DD and SGC researchers worked together to develop
an active and selective WDR5 “chemical probe” that could be used to test the
anti-leukemia hypothesis. After OICR and SGC scientists demonstrated this probe
could disrupt the interaction of WDR5 and MLL-1 in cells, they shared the
compound with academic investigators in Ontario and around the world, who
showed the probe could stop the growth of leukemia and other cancer cells.

Once the probe was
in the public domain, the OICR DD group seized the opportunity to
leverage its expertise to improve the drug-like properties and potency of the
probe, while creating novel intellectual property, in order to fully realize
its therapeutic and commercial potential. This subsequent development of the pre-clinical drug by OICR DD was made
possible by their extensive experience in the pharmaceutical industry and
academia, a
unique model that has helped to develop assets that are solid candidates
for investment and further development by industry partners. OICR DD is one of
the only industry-academic hybrid drug discovery teams in Ontario.

Over the next decade, pancreatic ductal adenocarcinoma (PDAC) – the most common type of pancreatic cancer – is projected to become the second leading cause of all cancer mortality. A better understanding of how PDAC changes when it metastasizes – or spreads from the pancreas to other organs – may help researchers find ways to treat the disease more effectively.

A study by OICR researchers and collaborators, published today in Cancer Cell, showed that the cells in advanced pancreatic tumours grow – or cycle – faster than those in early tumours, revealing one of the key reasons that the disease can advance so quickly. OICR’s Pancreatic Cancer Translational Research Initiative, PanCuRx, investigated the whole genomes and transcriptomes of more than 300 PDAC tumours, contrasting cells from primary tumours and cells from metastatic tumours. This distinction may help clinicians advise patients about treatment, whether it be surgery, chemotherapy or radiation.

“Often, a patient’s primary pancreatic cancer recurs
after surgery and chemotherapy, and there is limited knowledge of metastases to
guide the next course of action. In less common ‘metachronous’ cases, treatment
depends on whether the second tumour is new, or if it grew from remnants of a
previous tumour,” says Dr. Ashton Connor, chief resident in the General Surgery
training program at the University of Toronto and lead author of the study. “In
this study, we explored differences between primary and metastatic tumours in
the hopes of better understanding the mechanisms of cancer cell spread from the
pancreas, and to ultimately inform their treatment.”

Over the last decade, PanCuRx has assembled the
largest collection of genomic and transcriptomic data on primary and metastatic
PDAC tumours. The initiative continues to collect samples through the COMPASS
clinical trial today.

“There have been very few studies of advanced
PDAC, so our rich dataset is very valuable to the future of pancreatic cancer
research,” says Rob Denroche, bioinformatician, Project Leader of PanCuRx and co-author
of the study. “Research groups from Germany, Brazil, Japan and across North
America have been interested in the data that we’ve collected and we’re happy to
enable their discoveries.”

PanCuRx collaborations span four continents, largely due to their enriched dataset on metastatic PDAC.

Through COMPASS, PanCuRx will continue to build
on these findings and test if cell progression could be used to inform
treatment selection in the clinic.

“This work is foundational to
our understanding of advanced pancreatic cancer,” says
Dr. Steven Gallinger, PanCuRx Director and Head
of the Hepatobiliary/Pancreatic Surgical Oncology Program at UHN and Mount
Sinai Hospital. “We look forward to building on this understanding to better
inform treatment selection for those with this terrible disease.”

Personalized medicine presents a tremendous opportunity for molecular pathologists to contribute to improvements in detecting, diagnosing and selecting treatments for cancer patients. As new diagnostic and prognostic tools continue to emerge, it is becoming increasingly important for pathologists to engage in cancer research and understand new developments across scientific disciplines. Fostering this engagement begins with education.

OMPRN is championing the advancement of molecular pathology training across Canada through its engagement with the Royal College of Physicians and Surgeons of Canada (Royal College), Canada’s governing body for medical education. Together, they are developing a new curriculum for pathology residents based on competencies – the proficiency or ability to perform a skill – rather than the traditional time-based training approach where residents are evaluated based on the amount of time spent acquiring knowledge or practicing a skill.

Dr. David LeBrun, Principal Investigator at Queen’s Cancer Research Institute and Leader of OMPRN.

“The existing competencies around molecular pathology were not adequate in detail, nor were they adequate in rigour,” says Dr. David LeBrun, Principal Investigator at Queen’s Cancer Research Institute and Leader of OMPRN. “So we harnessed the opportunity to improve these training standards for the future of pathology in Canada.”

OMPRN developed a list of molecular pathology competencies, priorities and training strategies to inform a new national curriculum. These suggestions were presented to the Anatomical Pathology Specialty Committee of the Royal College, who accepted several of the proposed strategies and recognized OMPRN’s submission as an official Royal College Curricular Document – a curriculum guide for educators.

One of OMPRN’s major contributions to the new curriculum, which is currently being implemented across Canada, was a competency focused on synthesizing a unified, clinically-actionable report based on results from non-traditional diagnostic tests, such as liquid biopsies or genomic profiling. With this ability, pathologists can better inform clinicians while ensuring that there are no opportunities missed in the detection or diagnosis a patient’s disease.

“With proper training, pathologists can play a key role in bringing the benefits of new research discoveries into the patient experience,” says LeBrun. “These competencies will help ensure that treatment decisions in the clinic are well informed by both conventional pathology techniques and novel tools and resources.”

One of the key challenges of competency-based education is that some training centres may not have the expertise to train their residents on highly-specialized skills. OMPRN is working to address the gap in expertise by developing online education materials to complement the molecular pathology competencies and offering training courses like their inaugural Applied Molecular Pathology Course, which was held January 9-10 in Mississauga.

“Our mission is to create a vibrant community of cancer research-oriented pathologists in Ontario,” says LeBrun. “Through our educational initiatives, OMPRN is helping to build the next generation of pathologists and – in turn – driving the future of cancer innovation.”

For more information on the Ontario Molecular Pathology Research Network, please visit its website.

Learn more about the Royal College’s Competence by Design program in the video below.

On January 3, 23 community engagement professionals – including OICR’s Dr. Ann Meyer – were named AAAS Community Engagement fellows for 2019.

The Community Engagement Fellowship Program (CEFP) brings together professionals from a diverse range of scientific communities to share insights and develop strategies to strengthen their respective communities. CEFP aims to improve collaboration and community building in science – and that’s exactly what Meyer will continue to do in Canada’s bioinformatics space.

“Over the last few years, we’ve been working on filling the educational needs of Canada’s bioinformatics community,” says Meyer, Knowledge and Research Exchange Manager at OICR and Manager of Bioinformatics Education at bioinformatics.ca. “This fellowship will help us expand our efforts to foster and strengthen ongoing collaboration amongst research groups in Canada with similar interests.”

Meyer is the only individual from a Canadian institute who has been selected to participate in the CEFP since its inception. The 2019 cohort includes community leaders from the Chan Zuckerberg Science Initiative, the National Geographic Society and the Data Commons Pilot Phase Consortium.

“Alongside these talented community managers, I hope to bring back new techniques to better engage the bioinformatics community,” says Meyer. “Further developing our community will facilitate ongoing learning collaborations and strengthen this research network across our geographically disperse nation.”